2.1.1 Acromegaly

Suggested citation: The Endocrine Society. Endocrine Facts and Figures: Hypothalamic-Pituitary. First Edition. 2016

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Acromegaly is characterized by excess GH secretion and insulin-like growth factor 1 (IGF-1) concentrations, most commonly due to a pituitary adenoma.

2.1.1.1 Prevalence and Incidence

Table 13 summarizes available data on the prevalence of acromegaly. No incidence data were available.

Table 13. Prevalence of acromegaly.
POPULATION DATA SOURCE PREVALENCE PER 100,000 REFERENCE
US (n=123 million)

 

Administrative claims data 7.8 * Burton et al. 201676
Mexico (n=442)

 

The Acromegaly Clinic at Hospital de Especialidades in Mexico City 2.94 Mercado et al. 201477
UK (n=81,149) Sixteen general practitioner surgeries covering the area of Banbury. 8.6 Fernandez et al. 201074
UK (n=501) West Midlands Acromegaly Database  8.78 Sherlock et al. 200969
Abbreviations: US, United States; UK, United Kingdom.

Note: * Prevalence estimates increased with age, ranging from 29-37 cases per million among children aged 0-17 years old to 148-182 cases per million among adults aged 65 years and older. Males and females were similarly affected; each with approximately 77 cases per million each year.

2.1.1.2 Cost Burden

The economic burden of acromegaly in the US is largely unknown. One study, however, examined the associated healthcare costs of acromegaly in the US from data from claims databases between 2002 and 2009 for 2,171 acromegaly patients. In this study, results indicated that acromegaly has a mean healthcare cost of $24,900 per patient per year, with medical costs accounting for $17,715, and $7,185 accounting for pharmacy costs. Importantly, medical costs were primarily associated with non-emergency department outpatient services ($12,268), and inpatient hospitalization ($5,213).78

In addition, the presence of any complication statistically increased annual costs. In unadjusted comparisons to patients without complications, total costs were increased by $18,840 in patients with cardiovascular abnormalities, $16,701 in those with sleep apnea, $14,225 in those with colon neoplasms, %10,989 in those with musculoskeletal abnormalities, and $9,906 in those with hypopituitarism. Interestingly, costs were $2,610 lower in acromegaly patients with reproductive abnormalities than in those without. After adjusting for differences in age, gender, region, and cardiovascular risk factors, costs were increased by $8,401 in patients with colon polyps or colon cancer, by $7,502 in patients with musculoskeletal abnormalities, by $13,331 in those with cardiovascular abnormalities, by $10,453 in those with sleep apnea, and by $6,742 in those with hypopituitarism.78

2.1.1.3 Life Expectancy and Mortality

Table 14 presents mortality data on patients with acromegaly.

 Table 14. Mortality in patients with acromegaly.
POPULATION DATA SOURCE TYPE OF MORTALITY SMR OVERALL REFERENCE
UK (n=501) West Midlands Acromegaly Database

 

Overall 1.7 Sherlock et al. 200969
Prior radiotherapy 2.1
Prior ACTH deficiency 2.5
Prior gonadatropial deficiency 2.1
Mexico (n=442)

 

The Acromegaly Clinic at Hospital de Especialidades in Mexico City Overall 0.72 Mercado et al. 201477
Last GH above/below 2.5 ng/mL 1.5/0.44
Last GH above/below 1 ng/mL 1.17/0.16
Last IGF-1 above/below 1.2 times the upper limit of normal 0.94/0.46

Abbreviations: SMR, standardized mortality rate; n, number; US, United States; UK, United Kingdom.

2.1.1.4 Key Trends and Health Outcomes

 A recent study by Nachtigall et al. that included 100 patients at a neuroendocrine clinical center reported that primary care doctors play the major role in diagnosis of acromegaly, and that while 18% of patients present no symptoms at the time of diagnosis, acral changes (24%), and headaches (20%) are the most prevalent presenting symptoms prompting diagnosis.79

Due to the variable nature of the disorder, an individualized treatment is necessary.  However, the Endocrine Society 2014 Clinical Practice Guideline for Acromegaly provides evidence-based recommendations for the evaluation and management of acromegaly, including an algorithm for an integrated multidisciplinary therapeutic approach.80

Overall, the Endocrine Society Acromegaly Task Force suggests the following goals of management: 1) a biochemical target goal of an age-normalized serum IGF-1 value, 2) using a random GH < 1.0 ug/L as a therapeutic goal, and 3) maintaining the same GH and IGF-1 assay in the same patient throughout management.80

In terms of treatment strategies, the Task Force recommends transsphenoidal surgery as the primary therapy in most patients. However, in patients with parasellar disease making total resection unlikely, surgical debulking is suggested to improve subsequent response to medical therapy. Finally, medical therapy is recommended for patients with persistent disease following surgery, while radiation therapy is suggested in cases of residual tumor mass following surgery, or in cases where medical therapy is unavailable, unsuccessful, or not tolerated. For more detailed information please refer to the Endocrine Society 2014 Clinical Practice Guideline for Acromegaly.80

Recently, Broder et al. reported that out of 2,171 acromegaly patients, 77.8% received the majority of their care from non-endocrinologists, and 30.8% used pharmacologic treatment.78 Table 15 summarizes the monitoring tests and treatments used by these patients during the 12-month study period.

Table 15. Test and treatments for acromegaly used during a 12-month study period.
POPULATION TEST OR TREATMENT PERCENTAGE (%)
2,171 acromegaly patients (mean age: 45.3 years; 49.7% female)

 

 

 

 

 

 

 

 

 

 

Biochemical monitoring tests 56
     IGF-1 53.7
     GH 31.7
Acromegaly treatment N/A
     Surgery 5.3
     Radiation 2.3
Pharmacological treatment 30.8
     Octreotide long-acting release 18.6
     Dopamine agonists 9.8
     Octreotide short-acting 4.7
     Pegvisomant 4.1
     Lanreotide 1.2
Abbreviations: IGF-1, insulin-like growth factor-1; GH, growth hormone; N/A, not available.
Note: individual patients could have more than one type of test or treatment. For example, of patients receiving pharmacological therapy, 78% used only one treatment, 19.3% used two, 2.5% used three, and 0.1% used 4 types of treatment during the study year.  In the case of monitoring tests, 56% of patients has at least 1 IGF-1 or GH test, 53.7% had ≥ 1 IGF-1, and 31.7% had ≥ GH test.

Source: Broder et al. 201478

In terms of complications related to acromegaly, the most common are musculoskeletal abnormalities (25.6%), hypopituitarism (16.6%), sleep apnea (11.5%), cardiovascular abnormalities (10.3%), reproductive system abnormalities (9.3%), and colon neoplasms (6.6%). In addition, cardiovascular risk factors have been reported in 47.6% of patients: hypertension (31%), hypertriglyceridemia (19.8%), and diabetes (17.5%). When conducting unadjusted comparisons, inpatient hospitalizations increased in patients presenting any complication, except in the case of reproductive abnormalities, which were related to a decrease in hospitalization. Similarly, in comparison to patients without complications, emergency department visits were more common in patients with cardiovascular disease, musculoskeletal conditions, and hypopituitarism. After adjusting for differences in age, gender, region, and cardiovascular risk factors, musculoskeletal abnormalities increased the odds of hospitalization (odds ratio [OR]: 1.76), as did cardiovascular abnormalities (OR: 2.93), and sleep apnea (OR: 1.56). Further, the odds of an emergency department visit increased with musculoskeletal (OR: 1.87), and cardiovascular abnormalities (OR: 2.32).78

References

  1. Chung T, Monson J. Hypopituitarism [Updated 6 Feb 2015]. In: De Groot L, Beck-Peccoz P, Chrousos G, eds. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-
  2. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine S. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609.
  3. Corenblum B. Hypopituitarism. 2011; http://emedicine.medscape.com/article/122287-overview – a0101. Accessed June 3 2015.
  4. Thomson Reuters, IPD Data Analytics. National Center for Health Statistics. National Hospital Discharge Survey. 2010. Accessed June 3, 2015.
  5. Regal M, Paramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). 2001;55(6):735-740.
  6. Fernandez-Rodriguez E, Lopez-Raton M, Andujar P, et al. Epidemiology, mortality rate and survival in a homogeneous population of hypopituitary patients. Clin Endocrinol (Oxf). 2013;78(2):278-284.
  7. Castinetti F, Reynaud R, Saveanu A, et al. [Clinical and genetic aspects of combined pituitary hormone deficiencies]. Ann Endocrinol (Paris). 2008;69(1):7-17.
  8. Castinetti F, Reynaud R, Saveanu A, Barlier A, Brue T. Genetic causes of combined pituitary hormone deficiencies in humans. Ann Endocrinol (Paris). 2012;73(2):53-55.
  9. Kelberman D, Rizzoti K, Lovell-Badge R, Robinson IC, Dattani MT. Genetic regulation of pituitary gland development in human and mouse. Endocr Rev. 2009;30(7):790-829.
  10. Takagi M, Ishii T, Inokuchi M, et al. Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism. PLoS One. 2012;7(9):e46008.
  11. de Graaff LC, Argente J, Veenma DC, Drent ML, Uitterlinden AG, Hokken-Koelega AC. PROP1, HESX1, POU1F1, LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Horm Res Paediatr. 2010;73(5):363-371.
  12. Dateki S, Fukami M, Uematsu A, et al. Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion. J Clin Endocrinol Metab. 2010;95(8):4043-4047.
  13. Reynaud R, Gueydan M, Saveanu A, et al. Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab. 2006;91(9):3329-3336.
  14. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(8):2330-2340.
  15. Ammirati M, Wei L, Ciric I. Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2013;84(8):843-849.
  16. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298(12):1429-1438.
  17. Fernandez A, Brada M, Zabuliene L, Karavitaki N, Wass JA. Radiation-induced hypopituitarism. Endocr Relat Cancer. 2009;16(3):733-772.
  18. Abu Dabrh AM, Asi N, Farah WH, et al. Radiotherapy Versus Radiosurgery in Treating Patients with Acromegaly: A Systematic Review and Meta-Analysis. Endocr Pract. 2015;21(8):943-956.
  19. Bostrom JP, Meyer A, Pintea B, et al. Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas: high local control and low toxicity. Strahlenther Onkol. 2014;190(12):1095-1103.
  20. Roland Linder DKaFV. Surgery of Pituitary Tumors in Germany: Hypopituitarism, Mortality, Costs and the Effect of Surgeon. The Endocrine Society’s 94th Annual Meeting and Expo, June 23–26, 2012 – Houston, TX 2012; http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2012.NP.16.MON-718. Accessed March 15, 2016.
  21. Bates AS, Van’t Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996;81(3):1169-1172.
  22. Bulow B, Hagmar L, Mikoczy Z, Nordstrom CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol (Oxf). 1997;46(1):75-81.
  23. Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet. 2001;357(9254):425-431.
  24. Svensson J, Bengtsson BA, Rosen T, Oden A, Johannsson G. Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab. 2004;89(7):3306-3312.
  25. van Bunderen CC, van Nieuwpoort IC, Arwert LI, et al. Does growth hormone replacement therapy reduce mortality in adults with growth hormone deficiency? Data from the Dutch National Registry of Growth Hormone Treatment in adults. J Clin Endocrinol Metab. 2011;96(10):3151-3159.
  26. Gaillard RC, Mattsson AF, Akerblad AC, et al. Overall and cause-specific mortality in GH-deficient adults on GH replacement. Eur J Endocrinol. 2012;166(6):1069-1077.
  27. Pappachan JM, Raskauskiene D, Kutty VR, Clayton RN. Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies. J Clin Endocrinol Metab. 2015;100(4):1405-1411.
  28. Burman P, Mattsson AF, Johannsson G, et al. Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality. Journal of Clinical Endocrinology & Metabolism. 2013;98(4):1466-1475.
  29. Sherlock M, Ayuk J, Tomlinson JW, et al. Mortality in patients with pituitary disease. Endocr Rev. 2010;31(3):301-342.
  30. Nielsen EH, Lindholm J, Laurberg P. Excess mortality in women with pituitary disease: a meta-analysis. Clin Endocrinol (Oxf). 2007;67(5):693-697.
  31. Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990;336(8710):285-288.
  32. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E. Hypopituitarism. Lancet. 2007;369(9571):1461-1470.
  33. Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med. 1989;70(262):145-160.
  34. Snyder PJ, Fowble BF, Schatz NJ, Savino PJ, Gennarelli TA. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med. 1986;81(3):457-462.
  35. Cohen-Inbar O, Ramesh A, Xu Z, Vance ML, Schlesinger D, Sheehan JP. Gamma knife radiosurgery in patients with persistent acromegaly or Cushing’s disease: long-term risk of hypopituitarism. Clin Endocrinol (Oxf). 2016;84(4):524-531.
  36. Fatemi N, Dusick JR, Mattozo C, et al. Pituitary hormonal loss and recovery after transsphenoidal adenoma removal. Neurosurgery. 2008;63(4):709-718; discussion 718-709.
  37. Webb SM, Rigla M, Wagner A, Oliver B, Bartumeus F. Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metab. 1999;84(10):3696-3700.
  38. Arafah BM, Kailani SH, Nekl KE, Gold RS, Selman WR. Immediate recovery of pituitary function after transsphenoidal resection of pituitary macroadenomas. J Clin Endocrinol Metab. 1994;79(2):348-354.
  39. Aimaretti G, Ambrosio MR, Benvenga S, et al. Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI). Growth Horm IGF Res. 2004;14 Suppl A:S114-117.
  40. Stochholm K, Gravholt CH, Laursen T, et al. Mortality and GH deficiency: a nationwide study. Eur J Endocrinol. 2007;157(1):9-18.
  41. Johannsson G, Nilsson AG, Bergthorsdottir R, et al. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab. 2012;97(2):473-481.
  42. Attanasio AF, Bates PC, Ho KK, et al. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status–3-year results from the HypoCCS Database. J Clin Endocrinol Metab. 2002;87(4):1600-1606.
  43. Di Iorgi N, Napoli F, Allegri AE, et al. Diabetes insipidus–diagnosis and management. Horm Res Paediatr. 2012;77(2):69-84.
  44. Maghnie M, Cosi G, Genovese E, et al. Central Diabetes Insipidus in Children and Young Adults. New England Journal of Medicine. 2000;343(14):998-1007.
  45. Di Iorgi N, Allegri AE, Napoli F, et al. Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases. J Clin Endocrinol Metab. 2014;99(4):1264-1272.
  46. Schreckinger M, Szerlip N, Mittal S. Diabetes insipidus following resection of pituitary tumors. Clin Neurol Neurosurg. 2013;115(2):121-126.
  47. Juul KV, Schroeder M, Rittig S, Norgaard JP. National Surveillance of Central Diabetes Insipidus (CDI) in Denmark: results from 5 years registration of 9309 prescriptions of desmopressin to 1285 CDI patients. J Clin Endocrinol Metab. 2014;99(6):2181-2187.
  48. Nemergut EC, Zuo Z, Jane JA, Jr., Laws ER, Jr. Predictors of diabetes insipidus after transsphenoidal surgery: a review of 881 patients. J Neurosurg. 2005;103(3):448-454.
  49. Kristof RA, Rother M, Neuloh G, Klingmuller D. Incidence, clinical manifestations, and course of water and electrolyte metabolism disturbances following transsphenoidal pituitary adenoma surgery: a prospective observational study. J Neurosurg. 2009;111(3):555-562.
  50. Agha A, Liew A, Finucane F, et al. Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency. Clinical endocrinology. 2004;60(6):688-693.
  51. Aimaretti G, Ambrosio MR, Di Somma C, et al. Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab. 2005;90(11):6085-6092.
  52. Ananthakrishnan S. Diabetes insipidus in pregnancy: etiology, evaluation, and management. Endocr Pract. 2009;15(4):377-382.
  53. Aleksandrov N, Audibert F, Bedard MJ, Mahone M, Goffinet F, Kadoch IJ. Gestational diabetes insipidus: a review of an underdiagnosed condition. J Obstet Gynaecol Can. 2010;32(3):225-231.
  54. Saborio P, Tipton GA, Chan JC. Diabetes insipidus. Pediatr Rev. 2000;21(4):122-129; quiz 129.
  55. Hadjizacharia P, Beale EO, Inaba K, Chan LS, Demetriades D. Acute diabetes insipidus in severe head injury: a prospective study. J Am Coll Surg. 2008;207(4):477-484.
  56. Timper K, Fenske W, Kuhn F, et al. Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study. J Clin Endocrinol Metab. 2015;100(6):2268-2274.
  57. Vande Walle J, Stockner M, Raes A, Norgaard JP. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf. 2007;2(3):232-238.
  58. Arima H, Oiso Y, Juul KV, Norgaard JP. Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study. Endocr J. 2013;60(9):1085-1094.
  59. Kennedy PG, Mitchell DM, Hoffbrand BI. Severe hyponatraemia in hospital inpatients. Br Med J. 1978;2(6147):1251-1253.
  60. Gross P, Reimann D, Neidel J, et al. The treatment of severe hyponatremia. Kidney Int Suppl. 1998;64:S6-11.
  61. Hannon MJ, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences. Eur J Endocrinol. 2010;162 Suppl 1:S5-12.
  62. Ragnarsson O, Mattsson AF, Monson JP, et al. The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients. Eur J Endocrinol. 2014;171(5):571-579.
  63. Sherlock M, O’Sullivan E, Agha A, et al. Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients. Postgrad Med J. 2009;85(1002):171-175.
  64. Patterson JH. The impact of hyponatremia. Pharmacotherapy. 2011;31(5 Suppl):5S-8S.
  65. Mohan S, Gu S, Parikh A, Radhakrishnan J. Prevalence of hyponatremia and association with mortality: results from NHANES. Am J Med. 2013;126(12):1127-1137 e1121.
  66. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-42.
  67. Jahangiri A, Wagner J, Tran MT, et al. Factors predicting postoperative hyponatremia and efficacy of hyponatremia management strategies after more than 1000 pituitary operations. J Neurosurg. 2013;119(6):1478-1483.
  68. Callahan MA, Do HT, Caplan DW, Yoon-Flannery K. Economic impact of hyponatremia in hospitalized patients: a retrospective cohort study. Postgrad Med. 2009;121(2):186-191.
  69. Sherlock M, Reulen RC, Alonso AA, et al. ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly. J Clin Endocrinol Metab. 2009;94(11):4216-4223.
  70. Deitelzweig S, Amin A, Christian R, Friend K, Lin J, Lowe TJ. Health care utilization, costs, and readmission rates associated with hyponatremia. Hosp Pract (1995). 2013;41(1):89-95.
  71. Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120(11 Suppl 1):S1-21.
  72. Levy A. Pituitary disease: presentation, diagnosis, and management. J Neurol Neurosurg Psychiatry. 2004;75 Suppl 3:iii47-52.
  73. Agustsson TT, Baldvinsdottir T, Jonasson JG, et al. The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol. 2015;173(5):655-664.
  74. Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf). 2010;72(3):377-382.
  75. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006;91(12):4769-4775.
  76. Burton T, Le Nestour E, Neary M, Ludlam WH. Incidence and prevalence of acromegaly in a large US health plan database. Pituitary. 2016.
  77. Mercado M, Gonzalez B, Vargas G, et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J Clin Endocrinol Metab. 2014;99(12):4438-4446.
  78. Broder MS, Neary MP, Chang E, Cherepanov D, Katznelson L. Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases. Pituitary. 2014;17(4):333-341.

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